Assessing memory representations in freely-behaving animals with calcium imaging via miniscopes

对于这项RTI拨款，我们要求获得支持，以获得“最先进的”加州大学洛杉矶分校微型镜（版本4）进行体内钙成像在自由行为的啮齿动物。这些微型内窥镜将是我们在莱斯布里奇大学（UofL）加拿大行为神经科学中心（CCBN）新兴的大脑成像核心的重要补充。拟议的成像设备将由CCBN的至少9名NSERC资助的系统神经科学家和UofL生物科学系的一名用户使用。所有用户都可以使用该设备并获得技术支持。加州大学洛杉矶分校的系统被要求有几个原因：1）在大脑区域进行钙成像的能力，如海马（HPC），而动物是自由行为的，这是一个重大的进步，增加了我们可以评估的功能范围; 2）它是任务灵活的; 3）可以在不同的大脑区域使用; 4）它是用户友好的;和5）它是这项技术最有信誉的系统。 UCLA成像系统在我们的几个研究项目中将是必不可少的，包括：1）使用相同或不同的空间信息评估快速新学习过程中形成的HPC表征，我们假设这些空间信息在内容和潜在的神经生物学机制上会有所不同。微型镜将用于确定在变化的条件下表征如何不同; 2）研究昼夜节律扰动对HPC功能的影响。微型显微镜将用于评估各种形式的昼夜节律扰动（即/轮班工作）对HPC表征的影响;以及3）哺乳动物大脑中的记忆功能似乎是由介导不同记忆功能的神经网络组织的，并且在该组织内，正常的思维和行为源于这些系统之间的合作和竞争相互作用。我们将探索多个记忆网络之间的相互作用的机制，在不同的实验条件下，使用微型显微镜来成像皮层下和皮层区域的活动。 增加使用UCLA-V4的体内钙成像将对我们的学员非常有益，因为：1）光学成像方法由于各种原因（包括可以收集大量数据，但需要较少的技术专业知识来运行和维护设备）而变得越来越受传统电生理方法的欢迎; 2）理解从微型望远镜收集的大量数据需要我们的学员将获得的计算技能;以及3）提高所产生的出版物的质量。所有这些方面将有利于我们的学员，因为他们追求在神经科学的竞争空间。 我们将利用这项技术来推进我们对行为如何通过暴露于特定事件而形成的知识，负责的神经网络以及支持这些功能的生化机制。我们的研究将使所有加拿大人受益，因为我们扩大了对正常和异常行为的理解。

For this RTI grant, we request support to obtain “state of the art” UCLA miniscopes (version 4) to conduct in-vivo calcium imaging in freely behaving rodents. These miniscopes will be a crucial addition to our emerging Brain Imaging Core at the Canadian Centre for Behavioural Neuroscience (CCBN) at the University of Lethbridge (UofL). The proposed imaging equipment will be used by at least 9 NSERC-funded system neuroscientists from the CCBN, and a user from the Department of Biological Sciences at the UofL. All users will have access and technical support to use this equipment. The UCLA system is requested for several reasons: 1) ability to do calcium imaging in a brain area, like hippocampus (HPC), while the animal is freely-behaving is a major advancement that increases the range of functions we can assess; 2) it is task-flexible; 3) can be used in different brain regions; 4) it is user friendly; and 5) it is the most reputable system for this technique. The UCLA imaging system will be essential in several of our research programs including: 1) assess HPC representations formed during rapid new learning using the same or different spatial information which we hypothesize will differ in content and underlying neurobiological mechanism. The miniscopes will be used to determine how the representations differ under changed conditions; 2) investigate effects of circadian rhythm perturbations on HPC function. The miniscope will be used to assess the impacts of various forms of circadian perturbations (i.e./ shift work) on HPC representations; and 3) memory function in the mammalian brain appears to be organized by neural networks mediating different memory functions and within this organization, normal thought and behaviour arise from cooperative and competitive interactions between these systems. We will explore the mechanisms of interactions amongst multiple memory networks using the miniscopes to image activity in subcortical and cortical regions under different experimental conditions. Adding in-vivo calcium imaging using UCLA-V4 will be highly beneficial to our trainees because: 1) optical imaging methods are becoming increasingly popular over traditional electrophysiological methods for various reasons including large amounts of data can be collected and yet less technical expertise is required to run and maintain the equipment; 2) making sense of the high volumes of data collected from the miniscopes requires computational skills which our trainees will receive; and 3) enhance the quality of publications generated. All of these aspects will be advantageous to our trainees as they pursue a competitive space in neuroscience. We will use this technology to advance our knowledge of how behaviour is shaped by exposure to specific events, the neural networks responsible, and the biochemical mechanisms supporting these functions. Our research will benefit all Canadians as we expand our understanding of normal and abnormal behaviour.